Project Summary/Abstract The renewal of this Program Project ?Pathobiology of the Enteric System? builds upon the significant advances and accomplishments achieved during the last cycle of this Program Project as well as on the extensive experience and significant record of accomplishments in the basic, clinical and translational research in gastrointestinal motility at the Mayo Clinic. This Program Project focuses on dysregulation of motility of the gastrointestinal tract in patients with diabetes and in animal models of diabetes. This renewal request includes three Projects and three Cores. Thus, considerable coordination and administrative effort is essential to manage this Program, requiring an Administrative Core. The Administrative Core will provide an administrative structure that will integrate all Projects and scientific Cores. It will ensure that advances made in individual projects are rapidly exploited by all Projects and scientific Cores. The Administrative Core will maximize progress and minimize costs by coordinating experiments across the matrix of Projects and Cores and ensuring that there is no duplication of activities and that the aims of the Program Project are met. The Administrative Core also is the chief interface with Mayo Clinic research administration and the NIDDK. The Administrative Core (Core A): (1) Ensures that adequate progress is made on all Projects and develops plans for future initiatives; (2) Supervises and coordinates the preparation of budgets and provides financial oversight; (3) Reviews and evaluates the cores; (4) Manages all issues and communications between relevant administrative entities at Mayo Clinic and extramural agencies including the NIDDK; (5) Coordinates the meetings of the Executive Committee of Administrative Core A, the Internal Advisory Committee and the annual meeting of the External Advisory Committee. Implementation and management of the Program Project will be facilitated through the leadership of the Principal Investigator, Dr. Gianrico Farrugia, through the Executive Committee by formal bimonthly meetings, and as needed, by video conferences and e-mails. Assessment of scientific progress and facilitation of collaboration between the Projects and Cores will be accomplished through the bimonthly meetings with the Executive Committee and with the Project Leaders of the individual projects and the Directors of the Epigenomics and Transcriptomics core (Core B) and Physiological Characterization and Data Integration core (Core C). Assessment of scientific progress will also be achieved by review of the meetings with the Internal Advisory Committee and by annual formal review of the Program by the External Advisory Committee.